Prospective, Non-randomised Phase Ⅱ Study of Simultaneous Integrated Boost Radiotherapy and Concurrent Nimotuzumab or Chemotherapy for Locally Advanced Esophageal Carcinoma
试验速览
- 阶段
- 2 期
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Pathological response rate
研究概览
简要总结
This prospective, non-randomized phase II study aims to compare radiotherapy and concurrent nimotuzumab with concurrent chemoradiotherapy to obtain a non-inferior pCR rate and pathological lymph node metastases rate in premise of lower toxicities in locally advanced esophageal cancer.
详细描述
In the era of IMRT and concurrent chemoradiotherapy, the 5-year overall survival of esophageal cancer increase from 10% to about 20%-40%, recurrence rate decrease from 80% to 50%-60%, and local recurrence remains to be the most important type of failure. What called for is to enhance local control without increasing toxicity to improve survival. The investigators have found effective and safe regimen of simultaneously integrated boost radiotherapy in previous study, which can achieve high dose in tumor area with avoid of normal tissues. However, a recent prospective study reported that neoadjuvant chemoradiotherapy resulted in much higher toxicities compares to neoadjuvant chemotherapy (46% vs. 15%, p= 0.04). Although chemoradiotherapy reached a higher pCR rate (28% vs. 9%, p=0.002), patients did not differ in survival in two groups.
Nimotuzumab is an humanized monoclonal antibody against EGFR. Radiotherapy combines Nimotuzumab reveals synergistic effect in head and neck cancers with lower toxicities as compared to concurrent chemoradiotherapy. Our previous study showed that EGFR expression rate were similar in esophageal cancer and head and neck cancers. Based on above results, the investigators design this study which aims to obtain a non-inferior pCR rate and pathological lymph node metastases rate in premise of lower toxicities.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 69 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of clinical stage T1-4aN0-1M1a untreated squamous esophageal carcinoma
- •Adequate organ function
- •No known history of drug allergy
排除标准
- •Known drug allergy
- •Insufficient hepatorenal function
- •Severe cardiovascular diseases, diabetes with uncontrolled blood sugar, mental disorders, uncontrolled severe infection, active ulceration which need intervention.
研究组 & 干预措施
Neoadjuvant nimotuzumab
Radiation：Patients undergo radiotherapy once daily 5 days a week for an average of 4.5 weeks in the absence of disease progression or unacceptable toxicity. IMRT simultaneous integrated boost is used to achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.14Gy once respectively.
Concurrent nimotuzumab: Patients may receive nimotuzumab 400mg per week which start from 1 week before radiotherapy and in the following 4 weeks after enrollment in the absence of disease progression or unacceptable toxicity.
Assessment of surgery: Patients eligible for surgery after multiple disciplinary consultation will receive esophagectomy after a 4-6 weeks break after chemoradiation in the absence of any contraindication.
干预措施: IMRT simultaneous integrated boost (Radiation)
Neoadjuvant nimotuzumab
Radiation：Patients undergo radiotherapy once daily 5 days a week for an average of 4.5 weeks in the absence of disease progression or unacceptable toxicity. IMRT simultaneous integrated boost is used to achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.14Gy once respectively.
Concurrent nimotuzumab: Patients may receive nimotuzumab 400mg per week which start from 1 week before radiotherapy and in the following 4 weeks after enrollment in the absence of disease progression or unacceptable toxicity.
Assessment of surgery: Patients eligible for surgery after multiple disciplinary consultation will receive esophagectomy after a 4-6 weeks break after chemoradiation in the absence of any contraindication.
干预措施: Nimotuzumab (Drug)
Neoadjuvant nimotuzumab
Radiation：Patients undergo radiotherapy once daily 5 days a week for an average of 4.5 weeks in the absence of disease progression or unacceptable toxicity. IMRT simultaneous integrated boost is used to achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.14Gy once respectively.
Concurrent nimotuzumab: Patients may receive nimotuzumab 400mg per week which start from 1 week before radiotherapy and in the following 4 weeks after enrollment in the absence of disease progression or unacceptable toxicity.
Assessment of surgery: Patients eligible for surgery after multiple disciplinary consultation will receive esophagectomy after a 4-6 weeks break after chemoradiation in the absence of any contraindication.
干预措施: Esophagectomy (Procedure)
Neoadjuvant chemotherapy
Radiation：Patients undergo radiotherapy once daily 5 days a week for an average of 4.5 weeks in the absence of disease progression or unacceptable toxicity. IMRT simultaneous integrated boost is used to achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.14Gy once respectively.
Concurrent chemotherapy: Patients may receive a dosage range of Paclitaxel from 45 to 60 mg/m2 and Nedaplatin 25mg/m2 per week which start from 1 week before radiotherapy and in the following 4 weeks after enrollment in the absence of disease progression or unacceptable toxicity.
Assessment of surgery: Patients eligible for surgery after multiple disciplinary consultation will receive esophagectomy after a 4-6 weeks break after chemoradiation in the absence of any contraindication.
干预措施: IMRT simultaneous integrated boost (Radiation)
Neoadjuvant chemotherapy
Radiation：Patients undergo radiotherapy once daily 5 days a week for an average of 4.5 weeks in the absence of disease progression or unacceptable toxicity. IMRT simultaneous integrated boost is used to achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.14Gy once respectively.
Concurrent chemotherapy: Patients may receive a dosage range of Paclitaxel from 45 to 60 mg/m2 and Nedaplatin 25mg/m2 per week which start from 1 week before radiotherapy and in the following 4 weeks after enrollment in the absence of disease progression or unacceptable toxicity.
Assessment of surgery: Patients eligible for surgery after multiple disciplinary consultation will receive esophagectomy after a 4-6 weeks break after chemoradiation in the absence of any contraindication.
干预措施: Paclitaxel (Drug)
Neoadjuvant chemotherapy
Radiation：Patients undergo radiotherapy once daily 5 days a week for an average of 4.5 weeks in the absence of disease progression or unacceptable toxicity. IMRT simultaneous integrated boost is used to achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.14Gy once respectively.
Concurrent chemotherapy: Patients may receive a dosage range of Paclitaxel from 45 to 60 mg/m2 and Nedaplatin 25mg/m2 per week which start from 1 week before radiotherapy and in the following 4 weeks after enrollment in the absence of disease progression or unacceptable toxicity.
Assessment of surgery: Patients eligible for surgery after multiple disciplinary consultation will receive esophagectomy after a 4-6 weeks break after chemoradiation in the absence of any contraindication.
干预措施: Nedaplatin (Drug)
Neoadjuvant chemotherapy
Radiation：Patients undergo radiotherapy once daily 5 days a week for an average of 4.5 weeks in the absence of disease progression or unacceptable toxicity. IMRT simultaneous integrated boost is used to achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.14Gy once respectively.
Concurrent chemotherapy: Patients may receive a dosage range of Paclitaxel from 45 to 60 mg/m2 and Nedaplatin 25mg/m2 per week which start from 1 week before radiotherapy and in the following 4 weeks after enrollment in the absence of disease progression or unacceptable toxicity.
Assessment of surgery: Patients eligible for surgery after multiple disciplinary consultation will receive esophagectomy after a 4-6 weeks break after chemoradiation in the absence of any contraindication.
干预措施: Esophagectomy (Procedure)
Radical nimotuzumab
Radiation：Patients undergo radiotherapy once daily 5 days a week for an average of 5.5 weeks in the absence of disease progression or unacceptable toxicity. IMRT simultaneous integrated boost is used to achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.14Gy once respectively.
Concurrent nimotuzumab: Patients may receive nimotuzumab 400mg per week which start from 1 week before radiotherapy and in the following 4 weeks after enrollment in the absence of disease progression or unacceptable toxicity.
干预措施: IMRT simultaneous integrated boost (Radiation)
Radical nimotuzumab
Radiation：Patients undergo radiotherapy once daily 5 days a week for an average of 5.5 weeks in the absence of disease progression or unacceptable toxicity. IMRT simultaneous integrated boost is used to achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.14Gy once respectively.
Concurrent nimotuzumab: Patients may receive nimotuzumab 400mg per week which start from 1 week before radiotherapy and in the following 4 weeks after enrollment in the absence of disease progression or unacceptable toxicity.
干预措施: Nimotuzumab (Drug)
Radical chemotherapy
Radiation：Patients undergo radiotherapy once daily 5 days a week for an average of 5.5 weeks in the absence of disease progression or unacceptable toxicity. IMRT simultaneous integrated boost is used to achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.14Gy once respectively.
Concurrent chemotherapy: Patients may receive a dosage range of Paclitaxel from 45 to 60 mg/m2 and Nedaplatin 25mg/m2 per week which start from 1 week before radiotherapy and in the following 4 weeks after enrollment in the absence of disease progression or unacceptable toxicity.
干预措施: IMRT simultaneous integrated boost (Radiation)
Radical chemotherapy
Radiation：Patients undergo radiotherapy once daily 5 days a week for an average of 5.5 weeks in the absence of disease progression or unacceptable toxicity. IMRT simultaneous integrated boost is used to achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.14Gy once respectively.
Concurrent chemotherapy: Patients may receive a dosage range of Paclitaxel from 45 to 60 mg/m2 and Nedaplatin 25mg/m2 per week which start from 1 week before radiotherapy and in the following 4 weeks after enrollment in the absence of disease progression or unacceptable toxicity.
干预措施: Paclitaxel (Drug)
Radical chemotherapy
Radiation：Patients undergo radiotherapy once daily 5 days a week for an average of 5.5 weeks in the absence of disease progression or unacceptable toxicity. IMRT simultaneous integrated boost is used to achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.14Gy once respectively.
Concurrent chemotherapy: Patients may receive a dosage range of Paclitaxel from 45 to 60 mg/m2 and Nedaplatin 25mg/m2 per week which start from 1 week before radiotherapy and in the following 4 weeks after enrollment in the absence of disease progression or unacceptable toxicity.
干预措施: Nedaplatin (Drug)
结局指标
主要结局
Pathological response rate
时间窗: Up to 1 year
Adverse events
时间窗: Up to 2 years
Pathological lymph node metastases rate
时间窗: Up to 1 year
R0 resection rate
时间窗: Up to 1 year
次要结局
- Overall survival (OS)(Up to 2 years)
- Disease-free survival (DFS)(Up to 2 years)
- Recurrence rate(Up to 2 years)
研究者
Zefen Xiao
Professor
Cancer Institute and Hospital, Chinese Academy of Medical Sciences